Monoamine oxidase (MAO) inhibitors are known to be important antidepressant and antihypertensive agents. Our initial studies indicate that N-cyclopropyl-N-arylalkyl amines, a class of potent MAO inhibitors, are suicide inactivators of MAO. Experiments are designed to confirm the mechanism proposed for this irreversible inactivation. This includes gaining insight into the chemical mechanism of oxidation of monoamines catalyzed by MAO. In addition to enzymatic reactions using labeled substrates and inhibitors, non-enzymatic model reactions will be employed. The chemistry of oxidation of reversible inhibitors also will be investigate to assist in understanding the mechanisms of inactivation of the N-cyclopropyl-N-arylakyl amines and the oxidation pathway catalyzed by MAO. A compound will be tested as a new inactivator of MAO, designed to covalently attach to an active site residue other than flavin via a suicide inactivator mechanism. Also, a new class of potential MAO inactivators will be tested.